目标:洋甘菊茶,以其精致的味道而闻名,几个世纪以来,不仅因为它的味道,而且因为它的无数健康益处而受到赞赏。在这项研究中,我们通过关注洋甘菊(MatricariachamomillaL.)的抗炎活性,研究了其对癌症的预防潜力。
结果:从洋甘菊中对212种植物化学物质进行虚拟药物筛选,发现β-amyrin,β-eudesmol,β-谷甾醇,芹菜素,daucosterol,和杨梅素作为有效的NF-κB抑制剂。通过微尺度热电泳验证了计算机模拟结果,报告细胞系实验,和流式细胞仪测定活性氧和线粒体膜电位。通过使用NCI肿瘤细胞系面板将91种抗癌剂与已知的作用方式进行比较而产生的癌生物图显示了细胞毒性洋甘菊化合物的显着关系,lupeol,和槲皮素对微管抑制剂。使用α-微管蛋白-GFP转染的U2OS细胞以及羽扇豆醇和槲皮素与微管蛋白的分子对接,通过共聚焦显微镜验证了这一假设。两种化合物均诱导G2/M细胞周期停滞和坏死,而不是凋亡。有趣的是,羽扇豆醇和槲皮素不参与对已建立的抗癌药物(ABC转运蛋白,TP53或EGFR)。对NCI细胞系组的蛋白质组表达数据进行分层聚类分析,确定了两组40种蛋白质,确定了对羽扇豆醇和槲皮素的敏感性和抗性,进一步指出洋甘菊化合物的多特异性。此外,lupeol,槲皮素,β-amyrin抑制NF-κB报告细胞(HEK-BlueNull1)中促炎细胞因子IL-1β和IL6的mRNA表达。此外,以NF-κB作为这些化合物的靶蛋白的基于Kaplan-Meier的存活分析通过挖掘具有7489名癌症患者的基于TCGA的KM-Plotter库进行。肾透明细胞癌(3级,低突变率,低的新抗原载量)与患者生存期较短显著相关,表明这些肿瘤亚组可能受益于洋甘菊化合物对NF-κB的抑制。
结论:这项研究揭示了洋甘菊的潜力,将其定位为有前途的预防炎症和癌症的药物。建议进一步研究和临床研究。
OBJECTIVE: Chamomile tea, renowned for its exquisite taste, has been appreciated for centuries not only for its flavor but also for its myriad health benefits. In this study, we investigated the preventive potential of chamomile (Matricaria chamomilla L.) towards cancer by focusing on its anti-inflammatory activity.
RESULTS: A virtual drug screening of 212 phytochemicals from chamomile revealed β-amyrin, β-eudesmol, β-sitosterol, apigenin, daucosterol, and myricetin as potent NF-κB inhibitors. The in silico results were verified through microscale thermophoresis, reporter cell line experiments, and flow cytometric determination of reactive oxygen species and mitochondrial membrane potential. An oncobiogram generated through comparison of 91 anticancer agents with known modes of action using the NCI tumor cell line panel revealed significant relationships of cytotoxic chamomile compounds, lupeol, and quercetin to microtubule inhibitors. This hypothesis was verified by confocal microscopy using α-tubulin-GFP-transfected U2OS cells and molecular docking of lupeol and quercetin to tubulins. Both compounds induced G2/M cell cycle arrest and necrosis rather than apoptosis. Interestingly, lupeol and quercetin were not involved in major mechanisms of resistance to established anticancer drugs (ABC transporters, TP53, or EGFR). Performing hierarchical cluster analyses of proteomic expression data of the NCI cell line panel identified two sets of 40 proteins determining sensitivity and resistance to lupeol and quercetin, further pointing to the multi-specific nature of chamomile compounds. Furthermore, lupeol, quercetin, and β-amyrin inhibited the mRNA expression of the proinflammatory cytokines IL-1β and IL6 in NF-κB reporter cells (HEK-Blue Null1). Moreover, Kaplan-Meier-based survival analyses with NF-κB as the target protein of these compounds were performed by mining the TCGA-based KM-Plotter repository with 7489 cancer patients. Renal clear cell carcinomas (grade 3, low mutational rate, low neoantigen load) were significantly associated with shorter survival of patients, indicating that these subgroups of tumors might benefit from NF-κB inhibition by chamomile compounds.
CONCLUSIONS: This study revealed the potential of chamomile, positioning it as a promising preventive agent against inflammation and cancer. Further research and clinical studies are recommended.